Putting The Brakes On Bacteria.

Anyone who’s seen one of those milk-mustache commercials knows that humans need calcium. But scientists Matt Redinbo and Matt Wolfgang discovered that the mineral is vital for microbes as well: without calcium, some bacteria can’t move.

Bacteria use different strategies to get from place to place. Redinbo and Wolfgang were interested in a type of movement called twitching motility, in which bacteria use spiky extensions called pili to pull themselves around. “When the pili extend they can grab onto surfaces,” Wolfgang says. “They act like little grappling hooks so that when they retract, they can pull the bacteria forward.”

One bacterium that uses twitching motility is Pseudomonas aeruginosa. According to Wolfgang, this opportunistic pathogen is a major cause of hospital-acquired infections. Healthy individuals can live with Pseudomonas twitching around on them, but the bacterium can be deadly for people with weakened immune systems or patients with complicated wounds such as severe burns.

Redinbo and Wolfgang imagined that one way to reduce infections could be to stop the bacteria from moving onto people in the first place. The proteins that move pili are like small engines. If the protein equivalent of a piston could be removed, then the engine would stall and Pseudomonas would be stranded.

The two scientists started with a small protein called PilY1. Wolfgang’s lab showed that pili needed PilY1 in order to move and to infect a host, but no one knew why this was. Redinbo thought the team could learn more by figuring out the protein’s structure. His group crystallized pure PilY1 and then used special x-rays on the crystals to gather data about the protein’s shape and generate a picture of it.

The structure Redinbo’s group produced looked like a flower that was missing some petals. Redinbo had expected to see the flower shape, yet there was a peculiar feature that piqued his interest, he says: a calcium-binding site sitting in one of the flower petals.

Wolfgang and Redinbo thought it was a bit odd to find a calcium-binding site in a pili protein, so they decided to see what would happen if they stopped calcium from binding to PilY1. Using genetic manipulations and a process called calcium chelation, they reduced the amount of calcium in their Pseudomonas cultures. Without calcium, the bacteria couldn’t produce enough pili to move.

Both researchers were astounded. “Calcium ions are all over the place,” Redinbo says. “To see calcium in a protein was not a big surprise. To have calcium play this central a role in motility — that was a big surprise.”

Wolfgang says that calcium may be important for bacteria besides Pseudomonas. Other microbes including Neisseria gonorrhoeae, the bacterium that causes gonorrhea, have proteins that are similar to PilY1. Disrupting calcium binding could be a new angle to prevent disease transmission. Pseudomonas needs functional pili to traverse different environments, to attach to surfaces, and to find food. “That all hinges on a single atom,” Wolfgang says.

Meagen Voss received a master’s degree in neurobiology in spring 2010.

Matt Redinbo is a professor of chemistry and chair of the Department of Chemistry in the College of Arts and Sciences. Matt Wolfgang is an assistant professor in the Department of Microbiology and Immunology in the School of Medicine. This work appeared in Proceedings of the National Academies of Sciences in January 2010. Funding for the project came from the National Institutes of Health and the Howard Hughes Medical Institute.

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